D l t f Hi h D i R Diff ti l M bilit A l (DMA)Development of a High Dynamic Range Differential Mobility Analyzer (DMA)Development of a High Dynamic Range Differential Mobility Analyzer (DMA)Development of a High Dynamic Range Differential Mobility Analyzer (DMA)Development of a High Dynamic Range Differential Mobility Analyzer (DMA) p g y g y y ( )C l d ith M S t t d ESI SCoupled with a Mass Spectrometer and nano ESI SourceCoupled with a Mass Spectrometer and nano-ESI SourceCoupled with a Mass Spectrometer and nano-ESI SourceCoupled with a Mass Spectrometer and nano ESI Sourcep p

1 Á 1 1 2Mario Amo 1 Arturo Álvaro1 Ross McCulloch1 Juan Fernández de la Mora2Mario Amo,1 Arturo Álvaro1, Ross McCulloch1, Juan Fernández de la Mora2Mario Amo, Arturo Álvaro , Ross McCulloch , Juan Fernández de la Mora1SEADM S L Boecillo Spain; 2Yale University Mech Eng Dept New Haven CT 06520 8286 USA1SEADM S L Boecillo Spain; 2Yale University Mech Eng Dept New Haven CT 06520-8286 USASEADM S. L., Boecillo, Spain; Yale University, Mech. Eng. Dept., New Haven, CT 06520 8286, USA

O i T pes of Mobilit Peak TailingOverview R ltTypes of Mobility Peak Tailing h dOverview ResultsTypes of Mobility Peak Tailing Methods Resultsyp y g MethodsThere are several factors affecting ion solvation or ion adduction that decrease

Resultsd O i i ti C

MethodsThere are several factors affecting ion solvation or ion adduction that decreaseand Originating Causesthe dynamic range of ion mobility spectrometers such as the differential and Originating Causesthe dynamic range of ion mobility spectrometers such as the differential g g

mobility analyzers (DMA) After addressing each one of these factors themobility analyzers (DMA). After addressing each one of these factors theEff t f D i G T t d Fl t

y y ( ) gbilit k d i b i l i d til hi Effect of Drying Gas Temperature and Flowratemobility peak dynamic range can be progressively improved, until reaching Effect of Drying Gas Temperature and Flowrate 

Low Mobility Tailingy p y g p g y p , g

2 FWHM D i R f 105 Low Mobility Tailing2xFWHM Dynamic Ranges of ~105. 120ºC 140ºC 160ºCy g2xFWHM Dynamic Ranges of 10 . 120 C D i

140ºC i

160 C D i

Fi 4 e Drying gas Drying gas Drying gasFigure 4L M bilit T il d d b S l ti Add ti ng

y g gg

Compares real LowMobility Tails produced by Solvation or Adduction anCompares real y p y

RaIonization

I d ip

low and high 1 0 5 E 03 1.E+05c RIonization

Introduction low and high 1.0

y 

5.E‐03

L M bilit micStageIntroduction g

dynamic range ty 4 E 03LowMobility  am 3 lpm 1.5 lpm  3 lpm 

gIntroduction dynamic range sit 4.E‐03

Tail 1.E+04na 1 l3 lpm 

Drying gas Drying gas3 lpm Drying gas

mobility peaks of 0.8ns 3 E 03Tail 1.E 04

yn 1.5 lpm  Drying gas y g g3 lpm D i

y g g

Ion mobility spectrometry mass spectrometry (IMS MS) enables two mobility peaks of 0 8en 3.E‐03 D Drying gas Drying gasIon mobility spectrometry – mass spectrometry (IMS-MS) enables two- nitroglycerin-Cl-nt 2 03 1 E+03M  y g g

1.5 lpm(Ionization Source) Laminarizeddimensional separation [1] Two characteristics define the performance of the

nitroglycerin Cl0 6In 2.E‐03 1.E+03

HM 1.5 lpm 

Drying gas(Ionization Source) Laminarized

D l tidimensional separation [1]. Two characteristics define the performance of the m/z 262/46 0.6d  WH Drying gasDesolvating p [ ] p

i bilit ti d i d l ti I thi t d fm/z 262/46. ed 1.E‐03

1 E+02FWStageion mobility separation: dynamic range and resolution. In this study we focus ize 1.E+02xF

StageD i

y p y g yh d i d l h f f W d fi 0 4al

i 0.E+00 0 5 10 15 20 25 30 352xDrying gason the dynamic range, and evaluate the performance of our system. We define 0.4

ma 1275 1325 1375 1425 1475 1525 1575

0 5 10 15 20 25 30 35E i t bon the dynamic range, and evaluate the performance of our system. We define

rm Experiment numberthe 2xFWHM Dynamic Range as the ratio of the maximum peak intensity or

pNeutral Vaporsthe 2xFWHM Dynamic Range as the ratio of the maximum peak intensity 0.2N

o

G h 1 2 FWHM d i f i f d i d flNeutral Vapors

divided by the intensity of the low mobility tail 2 full widths (at half height) N

2xFWHMDynamic Range Graph 1. 2xFWHM dynamic range as a function of drying gas temperature and flowrate.Analyte Ionsdivided by the intensity of the low-mobility tail 2 full widths (at half height) 2xFWHM Dynamic Range bili k

p y g y g g pAnalyte Ions

away from the maximum (see figure 1) 0 0Mobility Peak = 320 (Paralell-plate)away from the maximum (see figure 1). 0.0y ( g )

1275 1325 1375 1425 1475 2xFWHM Dynamic Range 1275 1325 1375 1425 1475 y gMobility Peak = 1x10^5

DMA Voltage (V)Mobility Peak   1x10 5

Dynamic Range vs Loss of signal2xFWHMDynamic Range Definition DMA Voltage (V) e Dynamic Range vs. Loss of signal2xFWHM Dynamic Range Definition g ( )

nge y g gy g

1.E+06an2xFWHM Rac R

1 5 lpm 140ºCOriginating CausesFWHM 1.E+05mic 1.5 lpm. 140ºC Originating CausesFWHM

am Drying gasg g100 na 1 5 lpm 120ºC

Drying gas1 5 lpm 160ºC

l S l i i h h h A li f100

1.E+04yn 1.5 lpm. 120 C  1.5 lpm. 160ºC Figure 7. Sketch of the Desolvation-ESI ionization source, DMA and MS. The laminarExternal Solvation: Due to penetration through the DMA entrance slit ofs) 2xFWHM Dynamic1.E+04D Drying gas Drying gas

Figure 7. Sketch of the Desolvation ESI ionization source, DMA and MS. The laminar fl f h d d i ffi i l d l d l f h ESI iExternal Solvation: Due to penetration through the DMA entrance slit of

80ps 2xFWHM Dynamic 

M  Drying gas Drying gasflow of heated drying gas efficiently desolvates droplets from the nano-ESI, preventing

solvent micro-droplets incompletely desolvated within the nano-ES source80

(c Range = H/h 1 E+03HM

flow of heated drying gas efficiently desolvates droplets from the nano ESI, preventing t l f t i th DMAsolvent micro-droplets incompletely desolvated within the nano-ES source.y 

( Range = H/h 1.E+03

WHneutral vapors from entering the DMA.

60ity H FW

p gInternal Solvation or Adduction: From vapors and contaminants within thens

H1 E+02xFInternal Solvation or Adduction: From vapors and contaminants within the

40en

1.E+022x

closed DMA circuit They originate either from: AB S i QTRAP 5500 l d ith ll l l t DMA (SEADM40

nte

‐5% 0% 5% 10% 15% 20%closed DMA circuit. They originate either from: AB Sciex QTRAP 5500 was coupled with a parallel-plate DMA (SEADM,In

5% 0% 5% 10% 15% 20%y g AB Sciex QTRAP 5500 was coupled with a parallel plate DMA (SEADM,d l P5 ) hi h ld b i kl i ll d d d i h b ki20

I

Loss of Intensity Signal• The blower lubricant and shaft sealing model P5-e) which could be quickly installed and removed without breaking20 Loss of Intensity Signal• The blower lubricant and shaft sealing. model P5 e), which could be quickly installed and removed without breaking

h• Outgassing of DMA materials (gaskets and plastic materials) the MS vacuum The ion source was a custom nano-ESI source (50µm needle0 h Graph 2 Dynamic range as function of loss of intensity signal• Outgassing of DMA materials (gaskets and plastic materials). the MS vacuum. The ion source was a custom nano-ESI source (50µm needle,0 Graph 2. Dynamic range as function of loss of intensity signalg g (g p )

O t i f th t bi fitti fl t d l solution: MeOH H O 9:1 / HCl 0 1%) 1 5 L/min of heated drying gas‐100 ‐50 0 50 100 • Outgassing of the tubing, fittings, flowmeters and valves. solution: MeOH-H2O 9:1 / HCl 0.1%). 1.5 L/min of heated drying gasl ( )

Ou gass g o e ub g, gs, ow e e s a d va ves.I i i i h i l

2(99 95% purity nitrogen) was introduced symmetrically upstream of the DMADMA Voltage (V) • Impurities in the nitrogen supply (99,95% purity nitrogen) was introduced symmetrically upstream of the DMADMA Voltage (V) Impurities in the nitrogen supply. ( , p y g ) y y pi l t lit 2 5 L/ i f it (99 95%) i t d d t th i l tiinlet slit. 2.5 L/min of nitrogen (99,95%) was introduced to the recirculatingFigure 1 2xFWHM Dynamic Range Definition e s . .5 / o oge (99,95%) was oduced o e ec cu a gDMA d if i d f h MS i h h i

Figure 1. 2xFWHM Dynamic Range Definition

High Mobility Tailing DMA drift gas in order to compensate for the MS consumption through its C l iIn a low dynamic range differential mobility analyzer tails of high intensity High Mobility Tailing DMA drift gas in order to compensate for the MS consumption through its ConclusionsIn a low dynamic range differential mobility analyzer, tails of high intensity g y gorifice Conclusions

peaks hide low intensity peaks of other mobilities limiting the functionality oforifice. Co c us o s

peaks hide low intensity peaks of other mobilities, limiting the functionality of High Mobility Tailsp y p , g ythi t t hi h i l d t ti ( i l ti i fi 2) I bilit k bt i d b i th lt diff li dFi 5

High Mobility Tailsthis apparatus to high signal detection (see simulation in figure 2). Ion mobility peaks were obtained by scanning the voltage difference applied

A ll l l A l d i h d l i d SFigure 5. Shows Analyte Neutral Vapors Ionized Inside the DMApp g g ( g ) o ob y pea s we e ob a ed by sca g e vo age d e e ce app edb h DMA l Th d d l d f d i • A parallel plate DMA coupled with a desolvation stage and a nano-ESI sourceFigure 5. Shows

h th l t ´Analyte Neutral Vapors Ionized Inside the DMA

between the two DMA plates The standard analyte used for dynamic range A parallel plate DMA coupled with a desolvation stage and a nano ESI source how the analyte s4 E+035 E+06 ) between the two DMA plates. The standard analyte used for dynamic rangecan have a 2xFWHM dynamic range of 1x105 - a 300 X improvement over

yhigh mobility tail

4.E+035.E+06ps)

ps)

At h i A l i i L D i R S t calculations was nitroglycerin can have a 2xFWHM dynamic range of 1x10 - a 300 X improvement over high mobility tail cpcp Second Peak  AnalytePeakAtmospheric Analysis in a Low Dynamic Range System Figure 2 Red line calculations was nitroglycerin.our previous designstarts at the same 3.E+034.E+06 y 

(

y (

Charger ionAnalyte Peak3E+6 cps

p y y g y Figure 2. Red line h h bili our previous design.starts at the same

l h3.E+034.E+06

sity

sity Charger ion 3E+6 cps 1.0 shows the mobility

4 E 03

I d t d th t i i t th t i l d i th DMAp g

voltage as the most nsns

1.0

y 

yspectra of m/z

4.E‐03

In order to reduce the outgassing in our system, the materials used in the DMAvoltage as the most bil h i 2.E+033.E+06 tete First Peakity spectra of m/z o de o educe e ou gass g ou sys e , e a e a s used e

d i d if i i i l l l i T fl ® (PTFE d • Key factors for achieving this performance:mobile charger ion. Int

Int First Peak 

h i HighMobility0 8ns

p262/62 channel 3.E‐03

and its drift gas circuit were stainless steel, aluminum, Teflon® (PTFE and Key factors for achieving this performance:gTherefore ionization n 

I

n   Charger ion HighMobility 

A l t T il0.8en 262/62 channel and its drift gas circuit were stainless steel, aluminum, Teflon (PTFE and

D l d l b f h DMA liTherefore, ionization 2.E+032.E+06 IoIo

n Analyte Tail

nte

(nitroglicerin + 2.E‐03 InterferentPFA) and PEEK The only exception was the DMA blower shaft seal (material o Desolvate droplets before the DMA entrance slit.of the neutral te

 

er I

0 6In (nitroglicerin + i t f t)

2.E 03 InterferentPFA) and PEEK. The only exception was the DMA blower shaft seal (material o Desolvate droplets before the DMA entrance slit.

A id h i d i f l f h i i i i hof the neutral

l t i 8 E 021 E 06 lyt

ue0.6d  interferent). 1 E 03 unknown) To maintain its vapour emission concentrations as low as possible o Avoid the introduction of neutral vapors from the ionization region to theanalyte vapor is 8.E+021.E+06

nal

rgued

)Green and Blue

1.E‐03

NG (t t) unknown). To maintain its vapour emission concentrations as low as possible, o Avoid the introduction of neutral vapors from the ionization region to the A

y ptaking place inside Anha

riz Green and Blue NG (target)

and reduce the emission of lubricant from the bearings the blower was cooled DMAtaking place inside 0 E+000 E+00

A

Ch0.4al lines correspond to 0.E+00 and reduce the emission of lubricant from the bearings, the blower was cooled DMAthe DMA

0.E+000.E+00C

ma lines correspond to

i l i1275 1325 1375 1425 1475 1525 1575 g ,

i i t l Th bl t t i t i d b l 35ºC o The DMA system and the gas supply circuit made from low outgassingthe DMA.800 1000 1200 1400 1600rm nitroglycerin using an intercooler. The blower temperature was maintained below 35ºC, o The DMA system and the gas supply circuit made from low outgassing 800 1000 1200 1400 1600

DMAV l (V)0 2No nitroglycerin

bilit t g p ,h h DMA d 120ºC Th i materialsDMA Voltage (V)0.2N mobility spectra

whereas the DMA temperature was operated at 120ºC. The nitrogen materials.Ch I Cl 35/35 A l t I Nit l i 262/62Nitroglycerin Interferent

y palone (green) and whereas the DMA temperature was operated at 120 C. The nitrogen

o The contaminant emissions from the DMA blower minimizedCharger Ion Cl 35/35 Analyte Ion ‐ Nitroglycerin 262/620 0

Nitroglycerin Interferent alone (green) and recirculating circuit and all the fittings (Swagelok) were made of stainless o The contaminant emissions from the DMA blower minimized.0.0

Nitroglycerin interferent alone recirculating circuit and all the fittings (Swagelok) were made of stainless o The results obtained with 99 95% purity N2; high purity N2 not required1275 1325 1375 1425 1475Nitroglycerin interferent alone

(bl ) O i i ti C steel All valves were made of stainless steel with PFA or PEEK seatso The results obtained with 99,95% purity N2; high purity N2 not required.1275 1325 1375 1425 1475

C d S t (blue). Originating Causes steel. All valves were made of stainless steel with PFA or PEEK seats.DMA Voltage (V) Compound Spectra ( ) Originating CausesI d d i t t d l i t l t t bilit

DMA Voltage (V)

I i ti f t l l t th t t th DMA i • Increased drying gas temperature adversely impacts electrospray stability.I fi 2 th it l i k ( ) h k i t it 1 250 ti Ionization of neutral analyte vapors that enter the DMA via: Th t t f th d i dj t bl b t 70ºC d 220ºC

Increased drying gas temperature adversely impacts electrospray stability.In figure 2, the nitroglycerin peak (green) has a peak intensity 1.250 times Ionization of neutral analyte vapors that enter the DMA via: The temperature of the drying gas was adjustable between 70ºC and 220ºC,g , g y p (g ) p yl th it i t f t th t h th l l d th i

p y g g j ,d di h l l i i ilower than its interferent, that has the same molecular mass and the same main • Micro-droplets incompletely desolvated depending on the electrospray solution composition. i ilower than its interferent, that has the same molecular mass and the same main • Micro-droplets incompletely desolvated depending on the electrospray solution composition. Future research directionsfragments so it is not possible filter it in the mass spectrometer Looking at the • Small quantities of neutral vapors from the ionization region: The DMA

Future research directionsfragments, so it is not possible filter it in the mass spectrometer. Looking at the • Small quantities of neutral vapors from the ionization region: The DMAred line it is not possible to detect this concentration of nitroglycerin in air due

q p gt fl i t 100% ffi i t d t th ti f th d ift ithi C tl d l i i (D l ti L Fl SESI)red line, it is not possible to detect this concentration of nitroglycerin in air due counterflow is not 100% efficient due to the motion of the drift gas within Currently developing a new ion source (Desolvating Low Flow nanoSESI),

to the low dynamic range of the DMA (2xFWHM = 320) even when theg

th DMA lti i t i t fl j t (S fi 6)Currently developing a new ion source (Desolvating Low Flow nanoSESI),h ill ( l ) hto the low dynamic range of the DMA (2xFWHM = 320), even when the the DMA resulting in an asymmetric counterflow jet (See figure 6). that will operate as a nano-ESI or nano-SESI (vapor samples) source The newy g ( )

iti it f th DMA MS t i th ffi i t Fi 3 hthe DMA resulting in an asymmetric counterflow jet (See figure 6). that will operate as a nano ESI or nano SESI (vapor samples) source. The new

sensitivity of the DMA-MS system is more than sufficient. Figure 3, shows source will enable independent control of the temperatures in the electrosprayy y g ,th h th ti l it ti h th d i f th DMA t i

source will enable independent control of the temperatures in the electrospraythe same hypothetical situation when the dynamic range of the DMA system is and vapor ionization regions as well as the drying gas temperature resulting inthe same hypothetical situation when the dynamic range of the DMA system isi d 5 hi i i l i k 5 i l

and vapor ionization regions, as well as the drying gas temperature resulting inimproved to 1x105 In this scenario a nitroglycerin peak 1x10-5 times lower

p g y g g p gi d ES t bilitimproved to 1x10 . In this scenario a nitroglycerin peak 1x10 times lower improved ES stability.

than the interferent can be detectedp y

than the interferent can be detected.Cl-Cl

Atmospheric Analysis in a High Dynamic Range System Figure 3 Red line Atmospheric Analysis in a High Dynamic Range System Figure 3. Red line h i l d Cl-

1 0 shows a simulated Cl1.0

y  4.E‐03shows a simulated mobilit spect m A k l d tty mobility spectrum Interferent Acknowledgements0 8si 3 E‐03

y pof the m/z 262/62

Interferent Acknowledgements0.8en

3.E‐03 of the m/z 262/62 g

te channel in a high W f l D A l V hik f hi i i h f l int 2.E‐03 channel in a high

d i Nitroglycerine We are grateful to Dr. Anatoly Verenchikov for his many insightful suggestions0.6d 

I dynamic range g y We are grateful to Dr. Anatoly Verenchikov for his many insightful suggestions0 6

ed 1.E‐03y g

DMA system regarding the efficient coupling of a DMA to a mass spectrometerze DMA system. regarding the efficient coupling of a DMA to a mass spectrometer.0 4al

i

0 E+00 Nitroglycerin can 0.4

ma 0.E+00

1275 1325 1375 1425 1475 1525 1575Nitroglycerin can

References:rm 1275 1325 1375 1425 1475 1525 1575 be easily filtered by References:0 2or

be easily filtered by bilit f it 0.2N

o

Compound Spectra mobility from its [1]: J Rus; D Moro; J A Sillero; J Royuela A Casado J Fernández de la Mora IMS MS studies based onFigure 6 Ion trajectories when a single mobility is selected (intermediate mobility between

N Compound Spectra  yinterferent [1]: J. Rus; D. Moro; J.A. Sillero; J. Royuela, A. Casado, J. Fernández de la Mora, IMS-MS studies based on Figure 6. Ion trajectories when a single mobility is selected (intermediate mobility between (nitroglycerine and interferent.

coupling a Differential Mobility Analyzer (DMA) to commercial API-MS systems, Int. J. Mass Spectrom, 298,Figure 8 SEADM´s ionization source and DMA coupled to an ABcharger and analyte ions). Non-orthogonal counterflow in the original source configuration 0.0(nitroglycerine and i t f t) coupling a Differential Mobility Analyzer (DMA) to commercial API MS systems, Int. J. Mass Spectrom, 298,

30 40 (2010)Figure 8. SEADM s ionization source and DMA coupled to an AB charger and analyte ions). Non orthogonal counterflow in the original source configuration

ll t t th DMA th h diff i Hi h l it ithi th DMA 1275 1325 1375 1425 1475interferent)

30-40 (2010)Sciex QTRAP 5500 This was the configuration used in this workallows some vapors to enter the DMA through diffusion. High gas velocity within the DMA 1275 1325 1375 1425 1475 Sciex QTRAP 5500. This was the configuration used in this workp g g g ycreates a longitudinal component in the counterflow directionDMA Voltage (V) creates a longitudinal component in the counterflow direction.DMA Voltage (V)

63rd ASMS Conference on Mass Spectrometry and Allied Topics St Louis MD Missouri May 31 June 4 201563rd ASMS Conference on Mass Spectrometry and Allied Topics – St Louis MD, Missouri- May 31-June 4, 201563 ASMS Conference on Mass Spectrometry and Allied Topics St.Louis MD, Missouri May 31 June 4, 2015y y